Cellular and subcellular localization

Both galanin receptors show a widespread anatomical distribution throughout the central and peripheral nervous systems (Fig. 16.2). In 1986, both Melander et al. and Skofitsch et al. used receptor autoradiography to determine the distribution of [125I]-galanin binding sites in the rat CNS (Fig. 16.2) (Melander etal. 1986a; Skofitsch etal. 1986). Dense galanin binding was observed in the prefrontal cortex, the anterior nuclei of the olfactory bulb, several nuclei of the amygdaloid complex, the dorsal septal area, dorsal bed nucleus of the stria terminalis, the ventral pallidum, the internal medullary laminae of the thalamus, medial pretectal nucleus, nucleus of the medial optic tract, borderline area of the caudal spinal trigeminal nucleus adjacent to the spinal trigeminal tract, the substantia gelatinosa, and the superficial layers of the dorsal spinal cord. Moderate binding was observed in the piriform, periamygdaloid, entorhinal, insular cortex and the subiculum, the nucleus accumbens, medial forebrain bundle, anterior hypothalamic, ventromedial, dorsal premamillary, lateral and periventricular thalamic nuclei, the subzona incerta, Forel's field H1 and H2, periventricular gray matter, medial and superficial gray strata of the superior colliculus, dorsal parts of the central gray, peripeduncular area, the interpeduncular nucleus, substantia nigra zona compacta, ventral tegmental area, the dorsal and ventral parabrachial and parvocellular reticular nuclei. Mapping of galanin receptors was later performed in human post-mortem brain, and showed that the distribution is similar to that in the rat brain (Kohler and Chan-Palay 1990). However it is important to note that the primate and human brain has a higher density of galanin receptors than the rodent brain. Galanin receptors were also detected by autoradiography in the spinal cord and several peripheral tissues, such as the kidneys, the pancreas, the gastrointestinal tract, and the respiratory tract (Arvidsson et al. 1991; Waters and Krause 2000; Wiesenfeld-Hallin et al. 1992).

In the rat, GalR1 mRNA has been detected by Northern blot analysis in the brain, spinal cord and RIN14b cells. The GalR1 mRNA distribution in the rat CNS has been determined by in situ hybridization, which shows that rGalR1 expression occurs in areas where galanin and [125I]-galanin binding sites have been found previously, that is, in the hypothalamus (supraoptic nucleus), amygdala, ventral hippocampus, thalamus, brainstem (medulla oblongata, locus coeruleus and lateral parabranchial nucleus), and spinal cord (dorsal horn), showing a good agreement between mRNA and gene product data (Burgevin et al. 1995; Gustafson et al. 1996; Parker et al. 1995). The expression of GalR1 mRNA further shows plasticity. Hypothalamic GalR1 mRNA is elevated more in females than males, varies throughout the estrous cycle, and in the dorsal root ganglia of the spinal cord, GalR1 mRNA has been shown to increase after inflammation or peripheral nerve injury. Lactation and hypophysectomy, on the other hand, decrease GalR1 mRNA expression (Faure-Virelizier et al. 1998; Landry et al. 1998; Sten Shi et al. 1997). Similar binding profiles for GalR1 have been observed in [125I]-galanin bindning assays in humans and rats.

In comparison with rat GalR1, rat GalR2 mRNA is more widely distributed, with expression in many areas of the brain, where the highest levels are found in the hypothalamus, hippocampus, amygdala, piriform cortex, dentate gyrus, mammilary nuclei, and cerebellar cortex (Fathi et al. 1997; O'Donnell et al. 1999). Peripherally, rat GalR2 is found in the vas deferens, prostate, uterus, ovary, stomach, large intestine, dorsal root ganglia, and cells derived form the pancreas (Howard et al. 1997; O'Donnell et al. 1999; Sten Shi et al. 1997; Wang et al. 1997b). GalR2 has also been detected in the pituitary (Fathi et al. 1998a).

Northern blot studies of GalR3 mRNA initially showed that GalR3 mRNA is present in the heart, spleen, and testis (Wang et al. 1997a). Later, with the help of more sensitive methods, GalR3 transcripts were also detected in the CNS, with the highest levels in the hypothalamus and pituitary. Other regions, like the olfactory bulb, cerebral cortex, medulla oblongata, caudate putamen, cerebellum, and spinal cord, but not the hippocampus and substantia nigra, were also found to contain GalR3 mRNA (Smith et al. 1998). In the periphery, GalR3 mRNA is widespread, with existence in the liver, kidney, stomach, testicles, adrenal cortex, lung, adrenal medulla, uterus, vas deferens, choroid plexus, and dorsal root ganglia (Smith etal. 1998).

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